Early initiation of sirolimus will prevent or delay the development of intimal thickening and subsequent graft failure.

Treatment guided by the development of cardiac allograft vasculopathy (CAV) on intravascular ultrasound (IVUS) will be more effective in delaying progression of CAV compared to treatment guided by angiography.

Prevention of the development and progression of intimal thickness on IVUS will prevent the development of heart failure, graft dysfunction, and cardiovascular death related to CAV.

Small artery elasticity predicts progression of cardiac allograft vasculopathy and is modified by sirolimus

Patients who have no progression of CAV will have favorable improvement in biomarkers and endothelial cells compared to patients who have progression of CAV

Death from CAV, death from any cause, myocardial infarction, need for percutaneous coronary intervention (PCI), number of hospitalizations, infection rates, evidence of restrictive physiology, arrhythmic event related to CAV or pulmonary hypertension [ Time Frame: at 4 years. ] [ Designated as safety issue: No ]

Change in small artery elasticity [ Time Frame: At 1, 2, 3, and 4 years ] [ Designated as safety issue: No ]

Change in endothelial progenitor cell count [ Time Frame: At 1 and 2 years ] [ Designated as safety issue: No ]

Change in biomarkers [ Time Frame: At 1 and 2 years ] [ Designated as safety issue: No ]

Successful orthotropic heart transplant within 6 months to 3 years of enrolment

Less than moderate CAV by angiogram or IVUS

Exclusion Criteria

For Prospective Arm:

Greater than minimal baseline coronary disease

Chronic kidney disease with creatinine >2mg/dl

Baseline (1 month) ejection fraction < 50%

IV contrast allergy

Rejection within 3 months of enrollment

Sensitivity to sirolimus or its derivatives

Prior sirolimus use

Exclusion Criteria

For Retrospective Arm:

Significant baseline (one month) coronary artery disease (>50% in one or more vessels by angiogram or MIT >0.5 by IVUS)

Chronic kidney disease with creatinine >2mg/dl

Baseline (1 month) ejection fraction < 50%

IV contrast allergy

Rejection within 3 months prior to enrollment

Sensitivity to sirolimus or its derivatives

Prior sirolimus use

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305395

Locations

United States, Minnesota

Cardiology Division, University of Minnesota

Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota - Clinical and Translational Science Institute

Investigators

Principal Investigator:

Monica M Colvin-Adams, MD, MS

University of Minnesota - Clinical and Translational Science Institute